We have found that in frog erythrocytes the number of beta-adrenergic receptor recognition sites is greatly increased in the cytosol fraction when the cells are preincubated with (-) isoproterenol. This increase is agonist-specific and blocked by the presence of the incubation medium of a beta-adrenergic receptor antagonist, alprenolol. Concomittant with this agonist-induced increase, the number of membrane-bound beta-adrenergic receptor sites is reduced. There is a tight correlation between these two events. Neither process requires the new synthesis of RNA or protein. We have proposed that the recognition sites of this receptor are internalized from the plasma membrane into cytoplasm during desensitization of adenylate cyclase to beta-receptor stimulation and that this receptor internalization accounts for at least part of the receptor lost from the plasma membrane. The event of internalization is absolutely temperature and energy-dependent and diminished by cordycepin, an inhibitor of cyclic nucleotide dependent and independent protein kinases. The internalized receptor is sensitive to pronase but resistant to phospholipase. Unlike the membrane-bound beta-receptors, the binding affinity of the soluble receptors for the beta-adrenergic agonists is unaffected by the presence of guanylyl nucleotides.